Concordance and Diagnostic Accuracy of [¹¹C]PIB PET and Cerebrospinal Fluid Biomarkers in a Sample of Patients with Mild Cognitive Impairment and Alzheimer's Disease

Article type: Research Article

Authors: Leuzy, Antoine^a | Carter, Stephen F.^{a; b} | Chiotis, Konstantinos^a | Almkvist, Ove^{a; c} | Wall, Anders^d | Nordberg, Agneta^{a; e; *}

Affiliations: [a] Department NVS, Centre for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Karolinska Institutet, Huddinge, Sweden | [b] Wolfson Molecular Imaging Centre, University of Manchester, Manchester, United Kingdom | [c] Department of Psychology, Stockholm University, Stockholm, Sweden | [d] Section of Nuclear Medicine and PET, Department of Radiology, Oncology and Radiation Sciences, Uppsala University, Uppsala, Sweden | [e] Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden

Correspondence: [*] Correspondence to: Agneta Nordberg, MD, PhD, Division of Translational Alzheimer Neurobiology, Karolinska University Hospital Huddinge, Novum 5th Floor, Blickagången 6, S-141 57 Stockholm, Sweden. Tel.: +46 8 585 854 67; Fax: +46 8 585 854 70; E-mail: [email protected].

Abstract: Background:Alzheimer’s disease (AD) pathology can be quantified in vivo using cerebrospinal fluid (CSF) levels of amyloid-β1-42 (Aβ1-42), total-tau (t-tau), and phosphorylated tau (p-tau181p), as well as with positron emission tomography (PET) using [11C]Pittsburgh compound-B ([11C]PIB). Studies assessing concordance between these measures, however, have provided conflicting results. Moreover, it has been proposed that [11C]PIB PET may be of greater clinical utility in terms of identifying patients with mild cognitive impairment (MCI) who will progress to the dementia phase of AD. Objective:To determine concordance and classification accuracy of CSF biomarkers and [11C]PIB PET in a cohort of patients with MCI and AD. Methods:68 patients (MCI, n = 33; AD, n = 35) underwent [11C]PIB PET and CSF sampling. Cutoffs of >1.41 ([11C]PIB), <450 pg/mL—and a more lenient cutoff of 550 pg/mL—(Aβ1-42), <6.5 (Aβ1-42/p-tau181p), and 1.14 (Aβ1-42/t-tau), were used to determine concordance. Logistic regression was used to determine classification accuracy with respect to stable MCI (sMCI) versus MCI who progressed to AD (pMCI). Results:Concordance between [11C]PIB and Aβ1-42 was highest for sMCI (67%), followed by AD (60%) and pMCI (33%). Agreement was increased across groups using Aβ1-42 <550 pg/mL, or Aβ1-42 to tau ratios. Logistic regression showed that classification accuracy of [11C]PIB, between sMCI and pMCI, was superior to Aβ1-42 (73% versus 58%), Aβ1-42/t-tau (63%), and Aβ1-42/p-tau181p (65%). Conclusion:In the present study, [11C]PIB proved a better predictor of progression to AD in patients with MCI, relative to CSF measures of Aβ1-42 or Aβ1-42/tau. Discordance between PET and CSF markers for Aβ1-42 suggests they cannot be used interchangeably, as is currently the case.

Keywords: [¹¹C]PIB, Alzheimer's disease, amyloid, cerebrospinal fluid, mild cognitive impairment, positron emission tomography, tau

DOI: 10.3233/JAD-142952

Journal: Journal of Alzheimer's Disease, vol. 45, no. 4, pp. 1077-1088, 2015